15-99706737-G-C

Variant names:

• chr15-99706737-G-C
• rs325407
• NM_001319206.4:c.891G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001319206.4(MEF2A):​c.891G>C​(p.Gln297His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. Q297Q) has been classified as Benign.

• Frequency: Genomes: not found (cov: 30)
• Consequence: MEF2A NM_001319206.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.129
• Publications: 17 publications found

Genes affected

MEF2A (HGNC:6993): (myocyte enhancer factor 2A) The protein encoded by this gene is a DNA-binding transcription factor that activates many muscle-specific, growth factor-induced, and stress-induced genes. The encoded protein can act as a homodimer or as a heterodimer and is involved in several cellular processes, including muscle development, neuronal differentiation, cell growth control, and apoptosis. Defects in this gene could be a cause of autosomal dominant coronary artery disease 1 with myocardial infarction (ADCAD1). Several transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jan 2010]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEF2A	NM_001319206.4	c.891G>C	p.Gln297His	missense_variant	Exon 10 of 12	ENST00000557942.6	NP_001306135.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEF2A	ENST00000557942.6	c.891G>C	p.Gln297His	missense_variant	Exon 10 of 12	5	NM_001319206.4	ENSP00000453095.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 45

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.033	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	9.8
DANN	Uncertain	0.98
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.56	D
LIST_S2	Uncertain	0.89	D;D;D;.;D;D
M_CAP	Benign	0.037	D
MetaRNN	Uncertain	0.64	D;D;D;D;D;D
MetaSVM	Benign	-0.70	T
PhyloP100		-0.13
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-3.6	D;D;.;D;D;D
REVEL	Benign	0.27
Sift	Benign	0.032	D;D;.;D;D;D
Sift4G	Uncertain	0.060	T;T;T;T;D;D
Polyphen		0.0090	B;.;D;D;.;D
Vest4		0.70
MVP		0.36
MPC		0.39
ClinPred		0.99	D
GERP RS		-6.0
gMVP		0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs325407; hg19: chr15-100246942;